To perform ligand-dependent site-specific mutagenesis in the liver, we established transgenic mice expressing the tamoxifen-inducible Cre-ERT recombinase (Feil et al., 1996; Brocard et al., 1997) under the control of the human 1-antitrypsin (AT) promoter (Fig. 1) that is specifically active in hepatocytes (Jallat et al., 1990). Out of 20 transgenic founder animals, three lines expressing Cre-ERT in the liver, but not in the other tested organs, were obtained (Fig. 2A and data not shown). The expression pattern of Cre-ERT in the liver was analysed in the transgenic line exhibiting the highest Cre-ERT expression level. In situ hybridization as well as immunohistochemistry analysis revealed that Cre-ERT was expressed in approximately 40%–50% of the hepatocytes (Fig. 2B, C). Mosaic transgene expression using the AT promoter was previously reported (Ponder, 1996; Veniant et al., 1996). To analyse the recombinase activity, the AT-Cre-ERT transgenic line was crossed with reporter mice containing a loxP-flanked (floxed) allele of a target gene (Feil et al., 1997; Mascrez et al., 1998), and offspring harboring both the Cre-ERT and the floxed reporter allele were treated with tamoxifen. Excision occurred for 40%–50% of the reporter allele in the liver and was undetectable in all other organs analysed, as well as in oil-treated animals (Fig. 2D). Thus, recombination occurred in almost all hepatocytes expressing Cre-ERT. Taken together, our results show that the AT-Cre-ERT transgenic mice allow conditional site-specific somatic mutagenesis in the liver. The mosaic Cre-ERT expression in hepatocytes should be useful to produce genetic chimeras to study gene function during postnatal liver growth, regeneration, and carcinogenesis, and to perform genetic marking studies (Ponder, 1996).